The proposed work will further characterize the control of nuclear growth and asynchrony in cultured normal and neoplastic cells. Recent work has shown that tumor cell nuclei continue to multiply in the absence of cytoplasmic cleavage while normal cell nuclei are inhibited after one or two divisions. It was also shown that nuclei in multinucleated tumor cells become asynchronous and show pulverization while nuclei in multinucleated normal cells do not. Experimentation will further determine the capacity of tumor cell nuclei to multiply without cell division and analyze the controls present in normal cells. It will be shown if viral or chemical transformation of cultured normal cells results in a loss of these controls. Will full expression of this control loss require in vivo passage? Are DNA or RNA tumor viruses more effective in producing a loss of control? Further work will analyze the genetics of this control by the use of hybridization between normal human and malignant cells. In such hybrids, which nucleus is dominant? Further hybridization will identify the human chromosome(s) with oncogenic determinants if they exist. Pilot experiments will be performed to determine the therapeutic value of cytochalasin B, the substance which prevents cytoplasmic division.